Regional myocardial blood flow measurement technics will be thoroughly validated by comparing the results of simultaneous regional flow measurements performed in anesthetized open-chested dogs under control as well as under extreme conditions of coronary flow using the radioactive microsphere and constant-rate tritiated water infusion technics, whose underlying assumptions are quite different. Using animal models in which the hemodynamic and mechanical factors controlling transmural myocardial blood flow, e.g., heart rate (duration of diastole), coronary perfusion pressure and left ventricular (LV) end pressure are all maintained at their control level as well as animals with subendocardial underperfusion, it is intended to determine the direct action of nitroglycerin on the coronary vasculature as well as the time course of its action by means of sequential microsphere injections and the tritiated water technic. The degree of perfusion heterogeneity present in dogs with experimentally produced LV hypertrophy under control conditions and in the presence of subendocardial ischemia produced by an aortopulmonary shunt with cardiac pacing or by ventricular fibrillation on cardiopulmonary by-pass will be compared to that in normal dogs using both flow measurement technics. In addition, the degree of edema present in subendocardial ischemia, as well as the role of edema in production of this ischemia, will be determined in both dogs with normal and hypertrophied hearts and the possible benefits of continous infusions of nitroglycerin, hypertonic mannitol or propranolol in ameliorating the ischemia will be investigated. An extensive study of the LV baroreceptors suggested to us that their primary physiological role may be the control of regional myocardial function (contractility). It is intended to repeat this study in which the LV baroreceptors were stimulated by sudden distention of fluid-filled balloons in the LV adding simultaneous measurements of regional myocardial blood flow and of regional myocardial contractility in both animals with innervated and denervated hearts to test our hypothesis that regional perfusion/contractility relationships are controlled by the LV baroreceptors.